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Questions and Answers
Which of the following can trigger self-reactive T cells to be activated according to the concept of molecular mimicry?
Which of the following can trigger self-reactive T cells to be activated according to the concept of molecular mimicry?
Systemic lupus erythematosus (SLE) causes the immune system to attack healthy tissues.
Systemic lupus erythematosus (SLE) causes the immune system to attack healthy tissues.
True
Name one mechanism that contributes to immune privilege in certain tissues.
Name one mechanism that contributes to immune privilege in certain tissues.
Lack of lymphatic drainage, blood barriers, or immunosuppressive cytokines.
Apoptosis involves the activation of proteins called ______.
Apoptosis involves the activation of proteins called ______.
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Match the following factors with their association to systemic lupus erythematosus (SLE):
Match the following factors with their association to systemic lupus erythematosus (SLE):
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What is immune tolerance?
What is immune tolerance?
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Self-tolerance can be induced in both immature and mature lymphocytes.
Self-tolerance can be induced in both immature and mature lymphocytes.
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What are the two types of immunological tolerance mentioned?
What are the two types of immunological tolerance mentioned?
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What may happen to immature B cells if editing fails?
What may happen to immature B cells if editing fails?
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In the thymus, T cells that recognize self antigens with high avidity are ______.
In the thymus, T cells that recognize self antigens with high avidity are ______.
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Anergy occurs when developing B cells recognize self antigens weakly and become functionally responsive.
Anergy occurs when developing B cells recognize self antigens weakly and become functionally responsive.
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What happens to some self-reactive CD4+ T cells in the thymus?
What happens to some self-reactive CD4+ T cells in the thymus?
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What is peripheral tolerance in T cells?
What is peripheral tolerance in T cells?
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Anergy in T cells refers to their activation in response to an antigen.
Anergy in T cells refers to their activation in response to an antigen.
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What may happen to immature lymphocytes specific for self antigens in generative lymphoid organs?
What may happen to immature lymphocytes specific for self antigens in generative lymphoid organs?
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What are the two major factors that contribute to the development of autoimmunity?
What are the two major factors that contribute to the development of autoimmunity?
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Match the following terms with their definitions:
Match the following terms with their definitions:
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What are the two ligands recognized by PD-1?
What are the two ligands recognized by PD-1?
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Mature B lymphocytes that recognize self antigens in peripheral tissues may become functionally __________ or die by apoptosis.
Mature B lymphocytes that recognize self antigens in peripheral tissues may become functionally __________ or die by apoptosis.
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Match the following mechanisms of autoimmunity with their descriptions:
Match the following mechanisms of autoimmunity with their descriptions:
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Regulatory T cells produce IL-10 and ________, both of which inhibit immune responses.
Regulatory T cells produce IL-10 and ________, both of which inhibit immune responses.
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The process wherein mature lymphocytes die by ______ occurs during peripheral tolerance.
The process wherein mature lymphocytes die by ______ occurs during peripheral tolerance.
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Match the following T cell mechanisms with their functions:
Match the following T cell mechanisms with their functions:
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Which of the following statements about autoimmune diseases is true?
Which of the following statements about autoimmune diseases is true?
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What is receptor editing in immature B lymphocytes?
What is receptor editing in immature B lymphocytes?
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One of the general mechanisms of autoimmune reactions is adequate function of inhibitory receptors.
One of the general mechanisms of autoimmune reactions is adequate function of inhibitory receptors.
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What is the phenomenon called when an immune response against one self antigen leads to the activation of lymphocytes specific for other tissue antigens?
What is the phenomenon called when an immune response against one self antigen leads to the activation of lymphocytes specific for other tissue antigens?
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The engagement of inhibitory receptors on T cells generally promotes their activation.
The engagement of inhibitory receptors on T cells generally promotes their activation.
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What role do regulatory T cells play in the immune system?
What role do regulatory T cells play in the immune system?
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Study Notes
Immunological Tolerance and Autoimmunity
- Immunological Tolerance: The immune system's failure to respond aggressively to an epitope.
- Immune Self-tolerance: Results from inactivation or destruction of lymphocytes bearing BCRs and TCRs that recognize and bind self-antigens.
General Features of Immunological Tolerance
- Normal individuals tolerate their own antigens because lymphocytes recognizing self-antigens are killed, inactivated, or their specificity is altered.
- Self-tolerance can develop in immature lymphocytes of generative lymphoid organs (central tolerance) or in mature lymphocytes in peripheral tissues (peripheral tolerance).
- Central tolerance occurs during lymphocyte maturation in central lymphoid organs.
- Peripheral tolerance happens when mature lymphocytes recognize self-antigens and lose their ability to respond or undergo apoptosis, or are actively suppressed by regulatory T cells.
T Lymphocyte Tolerance: Central
- During T cell maturation in the thymus, many immature T cells recognizing self-antigens with high avidity are deleted (negative selection).
- Some self-reactive CD4+ T cells develop into regulatory T cells specific for these antigens in the thymus.
T Lymphocyte Tolerance: Peripheral
- Peripheral tolerance is the mechanism that renders mature T-cells recognizing self-antigens in peripheral tissues incapable of subsequent responses.
- Costimulation failure or lack of innate immunity can render mature CD4+ T cells unresponsive (anergy).
- Regulatory T cells can also suppress responses to self-antigens.
T Lymphocyte Tolerance: Mechanisms
- CTLA-4: A receptor of the CD28 family that inhibits T-cell responses by binding to B7 molecules with higher affinity than CD28 does.
- PD-1: Recognizes two ligands (PD-L1 and PD-L2) expressed by APCs and other tissue cells, leading to T-cell inactivation.
Suppression of Self-Reactive Lymphocytes by Regulatory T Cells
- Regulatory T cells produce IL-10 and TGF-β, which inhibit immune responses.
- TGF-β inhibits the proliferation and effector functions of T cells and activates macrophages. It also suppresses other cells like neutrophils.
- IL-10 inhibits the production of IL-12 by activated dendritic cells and macrophages - inhibiting IFN-γ. It also stops costimulatory and Class II MHC molecules from being expressed on dendritic and macrophage cells.
B Lymphocyte Tolerance: Central
- Immature B cells recognizing self-antigens with high affinity in bone marrow either adjust their specificity or are eliminated.
- Receptor editing: Genes responsible for BCR expression rearrange to produce a new receptor.
- Deletion: If editing fails, immature B cells can be eliminated.
- Anergy: Weakly self-reactive B cells become unresponsive (anergic) and leave the bone marrow.
B Lymphocyte Tolerance: Peripheral
- Mature B cells recognizing self-antigens in peripheral tissues may become unresponsive or undergo apoptosis in the absence of helper T cells.
- Inhibitory receptors set a threshold for B cell activation.
Autoimmunity
- Autoimmunity results from a failure of self-tolerance mechanisms, leading to an imbalance in lymphocyte activation and control.
- Defects in deletion (negative selection) of T or B cells, receptor editing in B cells, lack of regulatory T cells, or inadequate apoptotic functionality of self-reactive lymphocytes are potential causes.
- Genetic susceptibility and environmental factors influence autoimmunity.
Pathogenesis of Autoimmunity
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Infections or injuries can trigger autoimmune diseases.
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Autoimmune diseases can be systemic or organ-specific, depending on the distribution of the recognized autoantigens.
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Autoimmune diseases are often chronic, progressive, or self-perpetuating.
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Epitope spreading: A response to one self-antigen that damages tissue can cause other self-antigens to be released and cause the disease to worsen.
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Most autoimmune diseases are a complex polygenic trait.
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Microbes can activate Antigen-Presenting Cells (APCs) to show self-antigens and activate self-reactive T cells, thereby exacerbating the issue.
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Some microbial antigens can cross-react with self-antigens (molecular mimicry).
Immune Privileged Tissues
- Certain body sites, such as the eye, testis, brain, placenta, and fetus, do not develop immune responses.
- Mechanisms for immune privilege vary and include lack of lymphatic drainage, blood barriers, suppressive cytokines, and the expression of FasL and PD-L1.
Apoptosis
- Apoptosis is a regulated cell death process involved in physiological and pathological conditions.
- Two pathways (extrinsic and intrinsic) initiate apoptosis leading to caspase activation.
- Caspases fragment the nucleus and break down the cytoskeleton.
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Description
Test your knowledge on the mechanisms of T cell activation and the concept of immune tolerance, particularly in relation to systemic lupus erythematosus (SLE). This quiz covers topics such as molecular mimicry, immune privilege, and various forms of immunological tolerance affecting T cells and B cells. Dive into the intricacies of self-reactive T cells and their regulation in the immune system.